Network-Based In Silico Analysis of New Combinations of Modern Drug Targets with Methotrexate for Response-Based Treatment of Rheumatoid Arthritis

Background: Methotrexate (MTX), sulfonamides, hydroxychloroquine, and leflunomide have consistently resulted in remission with relatively mild to moderate adverse effects in patients with rheumatoid arthritis (RA). Modern medications outperform traditional treatments in that they target the pathological processes that underlie the development of RA. Methods: Following PRISMA guidelines, the authors accomplished a systematic review of the clinical efficacy of RA drugs, including the biologics such as Tumor Necrosis Factor-alpha inhibitors (TNF-α i) like Etanercept, Infliximab, Golimumab, and Adalimumab, kinase inhibitors (JAK inhibitors including Baricitinib and Tofacitanib), SyK inhibitors like Fos-tamatinib, MAPK inhibitors such as Talmapimod, T-cell inhibitors (Abatacept), IL6 blockers (Tocilizumab), and B cells depleters (Rituximab). These drugs have been found to increase remission rates when combined with MTX. A bioinformatics-based network was designed applying STRING-MODEL and the DrugBank database for the aforementioned drugs and MTX and, finally, employed for this systematic review. Results: Current research demonstrates that non-TNF-α inhibitor biologicals are particularly helpful in treating patients who did not respond well to conventional medications and TNF-α inhibitors. Despite being effective, these innovative drugs have a higher chance of producing hazardous side effects. The in silico investigations suggested an uncovered molecular interaction in combining MTX with other biological drugs. The STRINGMODEL showed that DHFR, TYMS, and ATIC, as the receptors of MTX, interact with each other but are not connected to the major interacted receptors. Conclusions: New game-changing drugs including Mavrilimumab, Iguratimod, Upadacitinib, Fenebrutinib, and nanoparticles may be crucial in controlling symptoms in poorly managed RA patients. Emerging therapeutic targets like Toll-like 4 receptors, NLRP3 inflammasome complexes, and mesenchymal stem cells can further transform RA therapy

Echoendoscopy-guided drainage of pancreatic collections using self-expanding metallic prosthesis: a retrospective observational cross-sectional study

Background: Pancreatic fluid collections are local complications of acute pancreatitis. Advances in research and the development of new techniques to address local complications have allowed minimally invasive therapeutic options. Endoscopic ultrasound-guided drainage is currently the procedure of choice. Objective: To describe the results of the placement of a self-expanding metallic prosthesis for echoendoscopy-guided drainage of pancreatic collections in patients. Methods: This study followed a retrospective observational cross-sectional model (STROBE rules). The study was sent and approved by the Institutional Ethics Committee of the Federal University of the State of Rio de Janeiro, Brazil. For data analysis, descriptive statistical analysis (mean and standard deviation), non-parametric analysis (Kruskal-Wallis, with p<0.05 with a statistical difference in CI95%), and parametric analysis (One-Way Anova, with p>0.05 with a statistical difference in CI95%), and logistic regression analysis, with p<0.05 with statistical significance in CI95%. Results: Thirteen patients were referred for drainage of collections, and 4 patients were excluded. Of the 9 patients studied, there was a predominance of males (7:2) with a mean age of 54.5 years. Eight patients had walled-off necrosis (WON). The device used was the Hot AxiosTM self-expanding luminal apposition metallic prosthesis, which was inserted uneventfully in all patients. Complete resolution of the condition was found in 88.8% of cases. After logistic regression analysis between the categorical predictors (Gender and Age) versus the response predictors (Necrosectomy, Review Interval, and Stent Permanence), it was observed that certain Gender or Age can influence the response predictors. Conclusion: Drainage of pancreatic collections using minimally invasive techniques is a safe and effective procedure

Does the Baroudi-Ferreira technique reduce seroma after abdominoplasty?

Introduction: Abdominoplasty has evolved over the years with improvement of techniques that initially had high complication rates. However, even with the evolution of operative techniques, seroma remains the most frequent early complication of this procedure. This study aims to compare the development of seroma after abdominoplasty with and without the use of quilting sutures. Methods: Twenty patients undergoing abdominoplasty were evaluated and divided into two groups: Group A (abdominoplasty using quilting sutures - Baroudi-Ferreira technique) and Group B (abdominoplasty without the use of quilting sutures). Results: Two patients in Group A (20%) had seroma, which was significantly lower (p = 0.05) than that in Group B, in which seven patients were diagnosed with seroma (70%). The mean volume observed in Group A was 26.5 mL, whereas in Group B, it was 146.5 mL. The highest volume aspirated in Group A was 130 mL, on the 15th postoperative day (POD), whereas in Group B it was 230 mL, on the 21st POD. Conclusion: In this study, the development of seroma in abdominoplasty was significantly lower in the group in which the Baroudi-Ferreira technique was used

Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient’s pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions

The Changing Environment in Postgraduate Education in Orthopedic Surgery and Neurosurgery and Its Impact on Technology-Driven Targeted Interventional and Surgical Pain Management : Perspectives from Europe, Latin America, Asia, and The United States

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work–life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur–investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management

Avaliação da qualidade de vida de pacientes portadores de hiperidrose primária submetidos à simpatectomia videotoracoscópica

RESUMO Objetivo: avaliar a qualidade de vida de pacientes submetidos à simpatectomia por videotoracoscopia para tratamento de hiperidrose primária. Métodos: foram avaliados os pacientes submetidos à simpatectomia por videotoracoscopia para tratamento de hiperidrose primária pela equipe de cirurgia torácica do Hospital Universitário Gafrée e Guinle-UNIRIO entre julho de 2004 e agosto de 2013. Foi aplicado um questionário sobre qualidade de vida relacionada à hiperidrose desde o pré-operatório até um ano após a operação. Resultados: o questionário foi aplicado em 122 pacientes com média de idade de 25 anos, sendo 57% mulheres. Quanto à severidade da hiperidrose primária, 83% dos pacientes referiam como pouco tolerável ou intolerável, associada com grande limitação da qualidade de vida, sendo esta pobre ou muito pobre em 82% dos casos. No pós operatório a hiperidrose compensatória ocorreu em 78% dos pacientes, entretanto foi considerada como imperceptível ou pouco perceptível por 85% destes pacientes, classificando-a como aceitável. Em 15% dos pacientes a hiperidrose compensatória foi classificada como perturbadora. Conclusão: a simpatectomia videotoracoscópica melhora a qualidade de vida dos pacientes com hiperidrose primária. A hiperidrose compensatória transitória ocorreu na maioria dos pacientes, mas não alterou de maneira significativa a melhora da qualidade de vida

Network-Based In Silico Analysis of New Combinations of Modern Drug Targets with Methotrexate for Response-Based Treatment of Rheumatoid Arthritis

Background: Methotrexate (MTX), sulfonamides, hydroxychloroquine, and leflunomide have consistently resulted in remission with relatively mild to moderate adverse effects in patients with rheumatoid arthritis (RA). Modern medications outperform traditional treatments in that they target the pathological processes that underlie the development of RA. Methods: Following PRISMA guidelines, the authors accomplished a systematic review of the clinical efficacy of RA drugs, including the biologics such as Tumor Necrosis Factor-alpha inhibitors (TNF-α i) like Etanercept, Infliximab, Golimumab, and Adalimumab, kinase inhibitors (JAK inhibitors including Baricitinib and Tofacitanib), SyK inhibitors like Fos-tamatinib, MAPK inhibitors such as Talmapimod, T-cell inhibitors (Abatacept), IL6 blockers (Tocilizumab), and B cells depleters (Rituximab). These drugs have been found to increase remission rates when combined with MTX. A bioinformatics-based network was designed applying STRING-MODEL and the DrugBank database for the aforementioned drugs and MTX and, finally, employed for this systematic review. Results: Current research demonstrates that non-TNF-α inhibitor biologicals are particularly helpful in treating patients who did not respond well to conventional medications and TNF-α inhibitors. Despite being effective, these innovative drugs have a higher chance of producing hazardous side effects. The in silico investigations suggested an uncovered molecular interaction in combining MTX with other biological drugs. The STRING-MODEL showed that DHFR, TYMS, and ATIC, as the receptors of MTX, interact with each other but are not connected to the major interacted receptors. Conclusions: New game-changing drugs including Mavrilimumab, Iguratimod, Upadacitinib, Fenebrutinib, and nanoparticles may be crucial in controlling symptoms in poorly managed RA patients. Emerging therapeutic targets like Toll-like 4 receptors, NLRP3 inflammasome complexes, and mesenchymal stem cells can further transform RA therapy

Single-port unilateral transaxillary totally endoscopic thyroidectomy: A survival animal and cadaver feasibility study

Background: Single-port unilateral axillary thyroidectomy has great potential to become a valid alternative technique for thyroid surgery. We tested the technique in a study on live animals and cadavers to evaluate the feasibility and reproducibility of the procedure. Materials and Methods: Institutional review board (IRB) approval was obtained in our university by the Council of Ethics for the study in surviving animals and cadavers. Subtotal thyroidectomy using unilateral axillary single port was performed in five dogs and five cadavers. Performing incision in the axillary fossa, a disposable single port was inserted. The dissection progressed for creating a subcutaneous tunnel to the subplatysmal region; after opening the platysma muscle and separation of the strap muscles, the thyroid gland was identified. After key anatomical landmarks were identified, the dissection was started at the upper pole towards the bottom, and to the isthmus. Specimens were extracted intact through the tunnel. Clinical and laboratorial observations of the experimental study in a 15-day follow-up and intraoperative data were documented. Results: All surgeries were performed in five animals which survived 15 days without postoperative complications. In the surgeries successfully performed in five cadavers, anatomical landmarks were recognised and intraoperative dissection of recurrent nerves and parathyroid glands was performed. Mean operative time was 64 min (46-85 min) in animals and 123 min (110-140 min) in cadavers, with a good cosmetic outcome since the incision was situated in the axillary fold. Conclusion: The technique of single-port axillary unilateral thyroidectomy was feasible and reproducible in the cadavers and animal survival study, suggesting the procedure as an alternative to minimally invasive surgery of the neck